Contribution of neuroimaging in the diagnosis of Alzheimer's disease and other dementias

This paper reviews the use of neuroimaging in the diagnosis of dementia, especially Alzheimer's disease. Computed tomography is still used to determine reversible causes of dementia; however, without clinical symptoms these causes are hard to find and computed tomography scanning is only cost-effective in a defined group of patients. Using magnetic resonance imaging, atrophy of the medial temporal lobe can be assessed volumetrically and visually, with a high correlation between the two methods. Medial temporal lobe atrophy is highly predictive of Alzheimer's disease, and correlates with neuropsychological performance and postmortem histologically measured volume. Cerebral volume changes over time seem to differentiate Alzheimer's disease and mild cognitive impairment progressing to Alzheimer's disease from controls with high accuracy. Studies of the corpus callosum in dementia indicate a cortico-cortical disconnection caused by atrophy. Of the new techniques, functional magnetic resonance imaging seems the most promising. This technique can possibly play a role in predicting Alzheimer's disease in patients with mild cognitive impairment. The use of single-photon emission computed tomography and positron emission tomography in (early) differential diagnoses seems limited. Lower regional cerebral blood flow is related to the severity of dementia and survival. Iodine-123 iodobenzamide single-photon emission computed tomography in dementia with Lewy bodies seems promising. Current and future positron emission tomography studies concentrate on memory function and receptor imaging. The focus in neuroimaging, especially magnetic resonance imaging, has shifted to early diagnosis and monitoring of the disease course, with a special interest in predicting dementia in patients with mild cognitive impairment.     

Visual rating and volumetry of the medial temporal lobe on magnetic resonance imaging in dementia: a comparative study

OBJECTIVES: It has been shown that atrophy of medial temporal lobe structures such as the hippocampus and entorhinal cortex shown on MRI may distinguish patients with Alzheimer's disease from healthy controls. However, the diagnostic value of visual inspection and volumetry of medial temporal lobe atrophy (MTA) on MRI in a clinical setting is insufficiently known. METHODS: Medial temporal lobe atrophy in 143 patients was visually rated from hard copies, using a 0-4 rating scale and a comparison was made with the volumes (cm(3)) of the medial temporal lobe as estimated with volumetry, using a stereological method. All patients were recruited in an unselected way in a clinical setting in the centre for memory impairments at the Huddinge University Hospital. Patients with Alzheimer's disease (n=41), patients with other dementias (vascular dementia, frontotemporal dementia, and unspecified dementia; n=36) as well as non-demented subjects (n=66) were included. Medial temporal atrophy and volumetry were evaluated as a diagnostic tool by performing logistic regression analysis including age, sex, and mini mental state examination (MMSE) score and calculating the sensitivity and specificity and percentage correct classification. RESULTS: Visual and volumetric analysis yielded statistically significant differences between patients with Alzheimer's disease and non-demented subjects, as well as between those with other dementias and non-demented subjects. Combining MMSE scores and visually rated MTA ratings yielded a sensitivity of 95% for Alzheimer's disease, 85% for other dementias. Non-demented subjects were identified with a specificity of 96%. Volumetry did not have an added value over the MMSE score alone. CONCLUSIONS: Visual rating of MTA is a clinically useful method for differentiating Alzheimer's disease from controls and is both quicker and more accurate than volumetry.     

A voxel based morphometry study on mild cognitive impairment

BACKGROUND: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer's disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. OBJECTIVE: To study the pattern of brain atrophy in MCI. METHODS: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p < 0.001. RESULTS: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere-for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. CONCLUSIONS: The MRI findings in MCI resemble those seen in early AD.     

Brain atrophy in frontotemporal dementia.

OBJECTIVES--To evaluate the pattern of regional brain atrophy in patients with frontotemporal dementia by comparing it with that in patients with Alzheimer's disease and normal controls. METHODS--Fourteen patients with frontotemporal dementia, 13 with moderate, and 33 with mild Alzheimer's disease, and 31 controls were studied. Atrophy was evaluated with linear measures in the anterior brain, medial temporal lobe, and hippocampal formation regions using MRI. RESULTS--Patients with frontotemporal dementia had greater atrophy in the anterior brain regions than patients with Alzheimer's disease or controls. Atrophy of the hippocampal formation, which best discriminates Alzheimer's disease from controls, was present also in patients with frontotemporal dementia. By contrast, atrophy of the medial temporal lobe, which is also present in Alzheimer's disease, was absent in frontotemporal dementia. CONCLUSION--A pattern of atrophy in the frontal lobes and hippocampal formation with sparing of the medial temporal lobe might be distinctive of frontotemporal dementia. Hippocampal involvement might not be specific for Alzheimer's disease and specific patterns of atrophy might be distinctive of some forms of degenerative dementia.     

Neuropsychological correlates of MRI measures in the continuum of cognitive decline at old age

OBJECTIVE: To investigate the independent associations between medial temporal lobe atrophy and white matter hyperintensities (WMH) and cognitive functions in the elderly. METHODS: Cognitive functions of 41 Alzheimer's disease patients, 20 patients with mild cognitive impairment and 28 elderly subjects without memory complaints were assessed using a neuropsychological test battery. Quantitative MRI measures of medial temporal lobe volume and WMH were obtained. Multiple regression analyses were performed to assess the independent contribution of MRI measures to impairment in several cognitive functions. RESULTS: Scores on the Wechsler Memory Scale and Trails B depended selectively on medial temporal lobe volume, whereas WMH selectively contributed to performance on Trails A. Medial temporal lobe volume and WMH both contributed to scores on the Cambridge Cognitive Examination and the Boston naming task. CONCLUSIONS: MRI measures suggestive of Alzheimer-type pathology and microvascular pathology independently contribute to cognitive decline at old age. Memory impairment as measured using the Wechsler Memory Scale and performance on Trails B primarily depended on medial temporal lobe atrophy. Psychomotor slowness, as measured using Trails A, mainly depended on WMH. These results suggest that vascular pathology and Alzheimer-type pathology each have specific cognitive correlates.     

Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment

To determine whether the medial temporal lobe is atrophic in subjects with mild cognitive impairment, and whether atrophy of this structure is a better predictor of dementia than memory dysfunction. Forty-five noninstitutionalized subjects aged 65–85 years were randomly selected from a population based study to obtain a sample with Alzheimer’s disease (AD; n = 7), and a clinically nondemented sample (n = 38). Twenty of the latter subjects displayed some cognitive impairment and fulfilled CAMDEX criteria for “minimal dementia.” Coronal T1-weighted magnetic resonance imaging was used to visualize the medial temporal lobe. The volume of the parahippocampal gyrus and hippocampus was measured, and medial temporal lobe atrophy was assessed qualitatively. The memory subscore from the CAMCOG was used as a measure of memory functioning. The follow-up period was 3 years. Nine subjects who were diagnosed as being minimally demented at baseline met the criteria for AD during follow-up. At baseline the volume of the parahippocampal gyrus of these subjects was smaller than that of the other subjects with minimal dementia. The memory score was the best predictor of clinical outcome. All medial temporal lobe measures increased the accuracy of prediction compared with only the memory score, by reducing the number of false-negative classifications of dementia. Severe medial temporal lobe atrophy is present even in some subjects with mild cognitive impairment and is an indicator of subsequent AD. The absence of medial temporal lobe atrophy, however, does not exclude the development of dementia. In the majority of subjects memory impairment was a better predictor of dementia than atrophy of the medial temporal lobe. The combination of the two increased predictive accuracy. Nondemented subjects with severe atrophy of the medial temporal lobe could be enrolled in drug trials aimed at slowing the progression of AD. Received: 18 June 1998 Received in revised form: 28 September 1998Accepted: 4 November 1998     

In vivo proton magnetic resonance spectroscopy of the temporal lobe in Alzheimer's disease

PURPOSE: Prior proton magnetic resonance spectroscopy (MRS) studies have consistently reported decreased brain n-acetyl aspartate (NAA) levels and increased myo-inositol (mI) levels in subjects with Alzheimer's disease (AD) relative to healthy comparison subjects. These studies have usually been conducted in small and homogeneous populations of patients with established Alzheimer's disease. Few studies have tested the usefulness of this finding in a general population seeking evaluation for memory loss and other cognitive declines. We designed a study to evaluate the significance of single-voxel proton MRS findings in these patients with memory loss and other cognitive declines. GENERAL METHOD: Thirty-five subjects with a primary complaint of memory loss and other cognitive declines were consecutively referred over a period of 13 months to a specialty clinic. Patients with a diagnosis of mild to moderate probable Alzheimer's disease (N = 22), non-Alzheimer's dementia (depression, multiinfarct dementia, Parkinson's Disease, Korsakoff's Psychosis, and bipolar disorder; N = 13), and healthy comparison subjects (N = 18) were examined with respect to possible differences in metabolites using proton MRS in a 3.4-ml anterior temporal lobe voxel. FINDINGS: The Alzheimer's disease group had 10.7% lower NAA/creatine (Cr) ratios relative to the healthy comparison group and 9.4% lower NAA/creatine relative to the non-Alzheimer's dementia group (15.0% lower NAA/creatine relative to the depression subgroup of the non-Alzheimer's dementia group). There were no significant differences in choline (Cho) or myo-inositol ratios among the groups. There were significant correlations between NAA/creatine ratios and mini-mental status exam (MMSE) scores in subjects with Alzheimer's disease (t = 2.41, p = 0.032) but not in subjects with non-Alzheimer's dementia or in its depression subgroup. CONCLUSIONS: This study found a reduction in the neuronal marker NAA in the anterior temporal lobe of patients diagnosed with probable Alzheimer's disease, using a short add-on proton MRS exam. This change was not observed in patients whose memory loss and other cognitive declines were not attributed to Alzheimer's disease, suggesting that it may aid in the diagnosis or detection of Alzheimer's disease.     

Temporal lobe rating scale: application to Alzheimer's disease and frontotemporal dementia

OBJECTIVES: Temporal lobe atrophy as assessed by MRI can be measured in several ways. Volumetric measurements are quantitative but very time consuming and require extensive training to perform, so are not easily transferable to clinical practice. Visual rating scales, by contrast, are quick and widely applicable. Although medial temporal lobe atrophy is well described in Alzheimer's disease (AD), it is uncertain how early these changes can be detected and whether they discriminate AD from other neurodegenerative diseases, most notably frontotemporal dementia (FTD). The objectives were (1) to develop a widely applicable temporal lobe rating scale, and (2) to characterise and quantify the patterns of temporal lobe atrophy in AD versus temporal and frontal variants of FTD. METHODS: The temporal lobe assessments were made using an established hippocampal rating scale extended to incorporate additional temporal regions. This was firstly validated with volumetric analysis and then applied to 30 probable AD, 30 FTD (consisting of 17 temporal variant (semantic dementia) and 13 frontal variant) and 18 control coronal MRI images. RESULTS: Bilateral hippocampal atrophy was found in 50% of the patients with AD. Contrary to expectations, patients with semantic dementia also had hippocampal atrophy, which for the left side exceeded that seen in AD; other regions (temporal pole, parahippocampal gyrus, and lateral temporal lobe), spared in AD, were severely atrophied in this group. The patients with frontal variant FTD occupied an intermediate position and were largely indistinguishable from AD. CONCLUSIONS: Hippocampal atrophy is, therefore, not specific for AD. Semantic dementia can be distinguished from AD, by the presence of severe bilateral atrophy of the temporal pole, parahippocampal and lateral regions. These findings have implications for the differential diagnosis of dementias.     

Hippocampal and temporal lobe atrophy and age-related decline in memory

OBJECTIVES: To evaluate the relationship of memory decline that accompanies aging with structural changes in the medial temporal lobe, in healthy middle-aged and older subjects. MATERIAL AND METHODS: A sample of 35 neurologically non-diseased subjects, between 55 and 70 years of age, were examined in a 5-year follow-up study. Neuropsychological investigation included tests of learning, verbal memory, and visual memory. MRI was performed with a superconducting MRI system operating at 1.0 T, using coronal slices of T1-weighted images. Medial temporal lobe atrophy was rated separately in the neocortical, entorhinal and hippocampal regions. RESULTS: We did not find any statistically significant relationship between mild hippocampal or temporal atrophy and memory test performance. Nor did the longitudinal decline in memory show a relationship with temporal lobe atrophy. CONCLUSIONS: The main outcome of our study was that age-related memory decline was not related to mild temporal lobe atrophy in healthy subjects without mild cognitive impairment. There could be other factors influencing memory functions besides age-related structural changes in temporal lobes.     

Do white matter changes contribute to the subsequent development of dementia in patients with mild cognitive impairment? A longitudinal study

OBJECTIVE: White matter lesions on brain CT or MRI are a frequent finding in patients with Alzheimer's disease. However, little is known about the prognostic significance of these changes in cognitively impaired individuals who are at risk for subsequent development of dementia. This study aims at investigating the potential impact of white matter lucencies (WML) on brain CT on the course of mild cognitive impairment. PATIENTS AND METHODS: Twenty-seven patients (mean age 72, SD 4.03) with mild cognitive impairment (MCI) and no signs of cerebrovascular disease were prospectively examined. At their initial presentation, all patients underwent a structured interview for the diagnosis of dementia (SIDAM) and a brain CT. Linear measures of atrophy and visual ratings of white matter changes were performed. At follow-up (mean interval 29 months), these patients were re-examined with the SIDAM. Eight patients had developed dementia and met clinical criteria for Alzheimer's disease (crossover group). RESULTS: Evaluation of the initial CT scans revealed significantly more frequent and extended white matter abnormalities and a higher degree of temporal lobe atrophy in the crossover group as compared to the cognitively stable group. In the crossover group, high WML severity initially was associated with a lesser degree of temporal lobe atrophy and higher global cognitive performance. CONCLUSION: We conclude that WML play a role in the dementia process and that they might accelerate cognitive decline in individuals with mild cognitive impairment. WML should be included in prospective studies of MCI as potential predictor variables.     

Blood pressure, white matter lesions and medial temporal lobe atrophy: closing the gap between vascular pathology and Alzheimer's disease?

BACKGROUND: Vascular factors are recognized as important risk factors for Alzheimer's disease, although it is unknown whether these factors directly lead to the typical degenerative pathology such as medial temporal lobe atrophy. We set out to investigate the relation between blood pressure and medial temporal lobe atrophy in patients with senile and presenile Alzheimer's disease with or without white matter lesions. METHODS: We determined the relation between blood pressure and pulse pressure and medial temporal lobe atrophy on MRI in 159 patients with Alzheimer's disease, stratified on white matter lesions and age at onset of dementia. RESULTS: There was a linear relation between systolic blood pressure and pulse pressure (both in tertiles) and the severity of medial temporal lobe atrophy (p(trend) = 0.05 and p(trend) 0.03, respectively). A significant relation was found between pulse pressure [beta = 0.08 (95% CI: 0.00-0.15; p = 0.05) per 10 mm Hg] and (borderline significant) systolic blood pressure [beta = 0.05 (95% CI: -0.01 to 0.11; p = 0.1) per 10 mm Hg] and medial temporal lobe atrophy. White matter lesions and age-stratified analysis revealed a significant association between systolic blood pressure and pulse pressure and medial temporal lobe atrophy, only in the subsample with white matter lesions and in the subsample with a senile onset of dementia. The relations were independent of severity of dementia and diabetes mellitus. CONCLUSIONS: Systolic blood pressure and pulse pressure are associated with medial temporal lobe atrophy in Alzheimer's disease, especially in the presence of white matter lesions and in patients with a late onset of dementia. Our finding may be another step in providing a rationale on how vascular factors could ultimately result in Alzheimer's disease.     

Medial temporal atrophy as a magnetic resonance imaging marker for Alzheimer's disease.

Medial temporal lobe atrophy (MTLA) on brain magnetic resonance imaging (MRI) may help differentiate Alzheimer's disease (AD) from multiinfarct dementia (MID) and other dementias. MTLA was seen in 6 of 11 patients with clinically diagnosed AD, 16 of 20 with mixed dementia (with both AD and MID), 1 of 5 with psychiatric disease, and in none of 32 with MID or 8 with other dementias (p less than 0.0001). Increased patchy periventricular signal, or "unidentified bright objects" were seen in 2 of 11 patients with AD, 10 of 20 patients with AD and MID, and 26 of 32 patients with MID. A larger series with autopsy correlation may verify that MTLA is a reasonably specific marker for AD, and unidentified bright objects are a sensitive, but not specific, marker for vascular dementias.     

Medial temporal lobe atrophy predicts Alzheimer's disease in patients with minor cognitive impairment

OBJECTIVES: To investigate whether medial temporal lobe atrophy predicted outcome in patients with minor cognitive impairment and whether assessment of the medial temporal lobe could increase the predictive accuracy of age and delayed recall for outcome. Quantitative and qualitative methods of assessing the medial temporal lobe were also compared. METHODS: Patients with minor cognitive impairment older than 50 years (n=31) were selected from a memory clinic and were followed up for on average 1.9 years. The medial temporal lobe was assessed in three different ways: volumetry of the hippocampus, volumetry of the parahippocampal gyrus, and qualitative rating of medial temporal lobe atrophy (MTA). Outcome measures were Alzheimer type dementia or cognitive decline at follow up. Delayed recall was tested with a verbal learning test. RESULTS: Ten patients had experienced cognitive decline at follow up, of whom seven had probable Alzheimer type dementia. All medial temporal lobe measurements were associated with cognitive decline at follow up (p trend analysis between 0.001 (hippocampus) and 0.05 (parahippocampal gyrus)). Only the hippocampal volume and MTA score were associated with Alzheimer type dementia at follow up (p trend analysis respectively 0.003 and 0.01). All medial temporal lobe measurements increased the predictive accuracy of age and the delayed recall score for cognitive decline (p increase in predictive accuracy varied between <0.001 (hippocampus) and 0.02 (parahippocampal gyrus and MTA score)) and the hippocampal volume and the MTA score increased the predictive accuracy of age and the delayed recall score for Alzheimer type dementia (p= 0.02). CONCLUSIONS: The ability to detect patients at high risk for Alzheimer type dementia among those with minor cognitive impairment increases when data on age and memory function are combined with measures of medial temporal lobe atrophy. Volumetry of the hippocampus is preferred, but qualitative rating of medial temporal lobe atrophy is a good alternative.     

Vascular cognitive impairment

Cerebrovascular disease is the second most common cause of acquired cognitive impairment and dementia and contributes to cognitive decline in the neurodegenerative dementias. The current narrow definitions of vascular dementia should be broadened to recognise the important part cerebrovascular disease plays in several cognitive disorders, including the hereditary vascular dementias, multi-infarct dementia, post-stroke dementia, subcortical ischaemic vascular disease and dementia, mild cognitive impairment, and degenerative dementias (including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies). Here we review the current state of scientific knowledge on the subject of vascular brain burden. Important non-cognitive features include depression, apathy, and psychosis. We propose use of the term vascular cognitive impairment, which is characterised by a specific cognitive profile involving preserved memory with impairments in attentional and executive functioning. Diagnostic criteria have been proposed for some subtypes of vascular cognitive impairment, and there is a pressing need to validate and further refine these. Clinical trials in vascular cognitive impairment are in their infancy but support the value of therapeutic interventions for symptomatic treatment.     

Healthy and pathological processes in adult development: new evidence from neuroimaging of the aging brain

PURPOSE OF REVIEW: Recent research has revealed that the population of older adults is composed not only of individuals who are either healthy or have an age-related disease, most commonly Alzheimer's disease, but also individuals with mild cognitive impairment who are at-risk for or already in the prodromal stage of Alzheimer's disease. These variations in cognitive aging can be related to their neural bases via structural and functional neuroimaging methods. RECENT FINDINGS: Healthy aging appears to primarily affect a frontal-striatal system that undergirds executive control of cognition, while minimally affecting medial temporal lobe structures. Functional imaging studies suggest that enhanced prefrontal engagement may offer compensatory plasticity that minimizes age-related cognitive losses. Mild cognitive impairment appears to affect the entorhinal cortex in particular, with functional consequences in other brain regions. Alzheimer's disease is characterized by severe hippocampal injury, although early-stage Alzheimer's disease may relatively spare some cortical regions. SUMMARY: Advances in in-vivo imaging methods are providing the tools for identifying different trajectories of neurocognitive aging, and knowledge about these brain changes may promote opportunities for treatment.     

Early thalamic and cortical hypometabolism in adult-onset dementia due to metachromatic leukodystrophy.

A case of early-onset adult dementia with family history of dementia is reported, characterised by neuropsychological deficits, suggesting frontal involvement, with mild non specific white matter abnormalities on CT scan. Familial Alzheimer's disease was suspected but the neuropathological diagnosis on brain biopsy was metachromatic leukodystrophy. 18FDG-PET revealed a very peculiar pattern of metabolic impairment in thalamic areas, in medial and frontopolar regions, and in occipital lobes. Neuropsychological follow-up showed relatively stable difficulties of long-term memory and signs of frontal lobe dysfunction, similar to those observed in subcortical dementias. MRI subsequently showed periventricular leukoencephalopathy. The brain metabolic pattern observed in that case of metachromatic leukodystrophy was quite different from that reported in other types of dementia.     

Hippocampal atrophy on MRI in frontotemporal lobar degeneration and Alzheimer's disease

BACKGROUND: Hippocampal atrophy on magnetic resonance imaging (MRI) is an early characteristic of Alzheimer's disease. However, hippocampal atrophy may also occur in other dementias, such as frontotemporal lobar degeneration (FTLD). OBJECTIVE: To investigate hippocampal atrophy on MRI in FTLD and its three clinical subtypes, in comparison with Alzheimer's disease, using volumetry and a visual rating scale. METHODS: 42 patients with FTLD (17 frontotemporal dementia, 13 semantic dementia, and 12 progressive non-fluent aphasia), 103 patients with Alzheimer's disease, and 73 controls were included. Hippocampal volumetry and the easily applicable medial temporal lobe atrophy (MTA) rating scale were applied to assess hippocampal atrophy. RESULTS: Multivariate analysis of variance for repeated measures showed an effect of diagnostic group on hippocampal volume. There was a significant diagnosis by side (left v right) interaction. Both FTLD and Alzheimer's disease showed hippocampal atrophy compared with controls. Results of the visual MTA rating scale confirmed these findings. Within the FTLD subtypes there were marked differences in hippocampal atrophy. Frontotemporal dementia and semantic dementia showed bilateral hippocampal atrophy, and in semantic dementia the left hippocampus was smaller than in Alzheimer's disease. No significant hippocampal atrophy was detected in non-fluent progressive aphasia. CONCLUSIONS: Hippocampal atrophy is not only a characteristic of Alzheimer's disease but also occurs in FTLD. The three clinical subtypes of FTLD show different patterns of hippocampal atrophy.     

Variability in blood-based amyloid-beta assays: the need for consensus on pre-analytical processing

The objective of this study was to examine the diagnostic accuracy of imaging and CSF biomarkers in clinically ambiguous dementia (CAD). 69 patients were prospectively followed. The endpoint was clinical diagnosis at follow-up of 24 months based upon existing criteria. Medial temporal lobe atrophy score on MRI, distinctive patterns on 99 mTc-HMPAO-SPECT, and CSF levels of amyloid-β peptide, total tau protein, and P-tau181P were used together with neuropsychological testing to assess Se (sensitivity) and Sp (specificity) of separate and combined markers. 60 patients reached the endpoint. A definite diagnosis was achieved in 48 patients. CSF biomarkers had a Sp of 71% and a Se of 100% for Alzheimer's disease (AD) diagnosis. Sp increased to 88% and 93% when MRI and MRI + SPECT were combined, at the expense of Se. CSF biomarkers levels also provided clues to frontotemporal (FTD) or vascular dementias (VaD) diagnosis when situated in an intermediate range between normal and pathological values. MRI and SPECT contributed mostly to the diagnosis of VaD (Se 88%, Sp 75%) and FTD (Se 73%, Sp 78%), respectively. Initial neuropsychological testing had a poor diagnostic accuracy, except for a neuropsychiatric inventory score >40 for the diagnosis of FTD (Se 73%, Sp 84%). Independent of the clinical diagnosis, medial temporal lobe atrophy and total-tau were best correlated with cognitive decline at 2 years. In conclusion, CSF biomarkers efficiently predict evolution toward an AD phenotype in CAD. Imaging biomarkers mostly contribute to the differential diagnosis between non-AD dementias. Initial neuropsychological testing was poorly contributive in CAD diagnosis.     

Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer's disease: insights from functional MRI studies

Functional MRI (fMRI) studies of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have begun to reveal abnormalities in memory circuit function in humans suffering from memory disorders. Since the medial temporal lobe (MTL) memory system is a site of very early pathology in AD, a number of studies, reviewed here, have focused on this region of the brain. By the time individuals are diagnosed clinically with AD dementia, the substantial memory impairments appear to be associated with not only MTL atrophy but also hypoactivation during memory task performance. Prior to dementia, when individuals are beginning to manifest signs and symptoms of memory impairment, the hippocampal formation and other components of the MTL memory system exhibit substantial functional abnormalities during memory task performance. It appears that, early in the course of MCI when memory deficits and hippocampal atrophy are less prominent, there may be hyperactivation of MTL circuits, possibly representing inefficient compensatory activity. Later in the course of MCI, when considerable memory deficits are present, MTL regions are no longer able to activate during attempted learning, as is the case in AD dementia. Recent fMRI data in MCI and AD are beginning to reveal relationships between abnormalities of functional activity in the MTL memory system and in functionally connected brain regions, such as the precuneus. As this work continues to mature, it will likely contribute to our understanding of fundamental memory processes in the human brain and how these are perturbed in memory disorders. We hope these insights will translate into the incorporation of measures of task-related brain function into diagnostic assessment or therapeutic monitoring, such as for use in clinical trials.     

Community based measures for managing mild cognitive impairment and dementia: the Osaki-Tajiri Project]

A cross-sectional study of aged patients with mild cognitive impairment in a local community was undertaken to investigate the clinical features of the condition, in addition to a longitudinal study to research its progression to cognitive deficit. Impairment of the basic functions of attention and executive function was confirmed, as opposed to impairment in the cognitive domain itself. Magnetic resonance imaging (MRI) findings showed a pattern close to that of healthy persons in their 80s, rather than that of patients with cognitive deficit. The results of the longitudinal study showed more progression to cognitive deficit when the clinical dementia rating was 0.5 in domains other than memory. No effects of lifestyle, internal diseases or psychosocial intervention were confirmed. In progression to Alzheimer's disease, generally low cognitive function and general atrophy were involved, whereas frontal lobe function, atrophy of the frontal and temporal lobes, white matter changes and cerebral infarction were related to progression to vascular dementia. Excessive dependence on primary prevention should be avoided for aged patients with mild cognitive impairment; rather, secondary prevention, using clinical dementia rating, psychological testing and MRI are desirable.